The active site of a number of metalloproteins contains a binoclear copper unit designated as "type 3" or EPR-nondetectable copper which exhibits unusual spectroscopic properties and interacts with oxygen as part of its biological function. This unit functions to bind oxygen (hemocyanin), to act as a two-electron oxidase (tyrosinase, laccase, and ceruloplasmin) and to hydroxylate organic substrates (tyrosinase). A series of protein derivatives has been prepared which allows the "type 3" copper active site to be systematically varied for spectroscopic study using a number of appropriate techniques. These studies have generated an effective picture of the oxyhemocyanin active site, provided a structural interpretation of the unusual spectroscopic properties and have demonstrated strong similarities between the active site in hemocyanin and tyrosinase. Chemical and spectroscopic studies are now proposed which should develop a detailed understanding of the properties of the "type 3" copper active site, how it activates oxygen and interacts with organic substrates, and how changes in site structure may contribute to inter-subunit cooperative interactions and to variation in biological function.